ABSTRACT
The behavioral and neurochemical effects of amitriptyline (10 mg/kg, i.p.) and fluoxetine (20 mg/kg, i.p.) after single and chronic administration in the setting of unpredictable mild stress in outbred ICR (CD-1) mice were studied. After a 28-day exposure to stress, we observed an increase in depressive reaction in a forced swim test in mice, as well as reduced hippocampal levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and an increased hypothalamic level of noradrenaline (NA). Single and chronic administration of amitriptyline and fluoxetine shortened the immobility period and increased the time corresponding to active swimming in the forced swim test. The antidepressant-like effect of fluoxetine - but not of amitriptyline - after a single injection coincided with an increase in the 5-HT turnover in the hippocampus. Chronic administration of the antidepressants increased the hypothalamic levels of NA. Thus, the antidepressant- like effect of amitriptyline and fluoxetine may result from an enhancement of the stress-dependent adaptive mechanisms depleted by chronic stress.
ABSTRACT
We studied the influence of intraperitoneal injection of ATP-sensitive potassium channels inhibitor glibenclamide in doses of 0.01, 0.1, 1, and 10 mg/kg on the effects of a new pyrazolo[C]pyridine derivative GIZh-72 (4,6-dimethyl-2-(4-chlorphenyl)-2,3-dihydro-1Hpyrazolo[ 4,3-C]pyridine-3-on, chloral hydrate; 20 mg/kg, intraperitoneally) in the marble burying and open-field tests in mice. It was found that glibenclamide produced an anxiolytic effect in the open-field test (in a dose of 0.01 mg/kg) and anticompulsive effect in the marble burying test (in doses of 1 and 10 mg/kg). The observed behavioral effects of glibenclamide did not depend on blood glucose level. At the same time, glibenclamide in subeffective (0.01 and 0.1 mg/kg) and effective (1 and 10 mg/kg) doses potentiated the psychotropic effects of GIZh-72 in these tests. It can be assumed that the psychotropic effects of GIZh-72 depend on functional activity of ATP-sensitive potassium channels.
Subject(s)
Anti-Anxiety Agents/pharmacology , Glyburide/pharmacology , KATP Channels/metabolism , Obsessive-Compulsive Disorder/drug therapy , Psychotropic Drugs/pharmacology , Pyrazoles/pharmacology , Pyridines/pharmacology , Animals , Blood Glucose/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Humans , Male , Mice , Mice, Inbred BALB C , Obsessive-Compulsive Disorder/metabolism , Obsessive-Compulsive Disorder/physiopathologyABSTRACT
The severity and specificity of CNS disturbances resulting from negative psychoemotional experience are determined by not only genetically determined stress sensitivity, but also epigenetic factors; among the latter, the context of stress exposure, e.g. stress controllability is considered. We examined the effect of controllability factor on behavioral and neurochemical parameters of acute stress in the elevated plus maze test. The situations of controllable and uncontrollable stress were modeled by allowing or restricting mice in their choice for closed arms during testing in the maze. The anxiety level of inbred BALB/c and C57Bl/6N mice was assessed and the levels and monoamine turnover in the medial prefrontal cortex, hippocampus, amygdala, and hypothalamus were measured. It was found that the decrease in stress controllability suppresses explorative activity in mice; the behavioral and neurochemical differences between the two strains are not constant feature and depend on stress controllability; serotoninergic and dopaminerigic neurotransmission in the hypothalamus can be a signal to discriminate stress controllability in the brain.
